A Study of Intravenous Oseltamivir [Tamiflu] in Infants With Influenza

An Open-label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir in the Treatment of Infants Less Than One Year of Age With Influenza Infection

This open-label study will assess the pharmacokinetics and safety of oseltamivir [Tamiflu] in 3 cohorts of infants, aged 0-30 days, 31-90 days and 91-<365 days with influenza infection. Patients will receive 10 doses of intravenous oseltamivir [Tamiflu] therapy over 5 or 6 days. Optional oral therapy with oseltamivir [Tamiflu] may be considered following the intravenous dose associated with pharmacokinetic blood sampling. Evidence of continued virus shedding at day 6 can allow for up to 5 additional days (10 doses) of oral or intravenous administration. Anticipated time on study drug is 5-11 days. Target sample size is <50 patients.

Study Overview

• Status: Terminated
• Conditions: Influenza
• Intervention / Treatment: Drug: Tamiflu

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 45229-3039
  • California
    • Los Angeles, California, United States, 90095
    • Oakland, California, United States, 94609-1809
    • Orange, California, United States, 92868
    • San Diego, California, United States, 92123
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Delaware
    • Wilmington, Delaware, United States, 19803
  • Florida
    • Jacksonville, Florida, United States, 32209
  • Illinois
    • Chicago, Illinois, United States, 60611
  • Indiana
    • South Bend, Indiana, United States, 46601
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
    • Boston, Massachusetts, United States, 02118
    • Boston, Massachusetts, United States, 02115
    • Springfield, Massachusetts, United States, 01199
  • Michigan
    • Detroit, Michigan, United States, 48201
  • Nebraska
    • Omaha, Nebraska, United States, 68131
  • New Jersey
    • Morristown, New Jersey, United States, 07960
    • New Brunswick, New Jersey, United States, 08901
  • New York
    • Bronx, New York, United States, 10461
    • Brooklyn, New York, United States, 11203
    • New York, New York, United States, 10016
    • Stony Brook, New York, United States, 11794
    • Syracuse, New York, United States, 13210
  • North Carolina
    • Durham, North Carolina, United States, 27705
    • Raleigh, North Carolina, United States, 27610
  • Ohio
    • Akron, Ohio, United States, 44308
    • Cleveland, Ohio, United States, 44106
    • Dayton, Ohio, United States, 45404
    • Toledo, Ohio, United States, 43606
    • Toledo, Ohio, United States, 43608
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
  • Texas
    • Austin, Texas, United States, 78723
    • Dallas, Texas, United States, 75390-9063
    • Houston, Texas, United States, 77030
  • Virginia
    • Richmond, Virginia, United States, 23292
  • Wisconsin
    • Madison, Wisconsin, United States, 53792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infant patients
• Date of birth to date of enrollment is <1 year
• Diagnosis of influenza
• Duration of influenza symptoms </=96 hours prior to first dose
• - Parent/guardian willing to have patient receive intravenous therapy for 3 or 4 days (5 or 6 doses of study drug)

Exclusion Criteria:

• Date of conception to date of birth + date of birth to enrollment is <36 weeks
• Creatinine clearance <30 mL/min/1.73m2
• Patients receiving any form of renal replacement therapy at baseline
• Clinical evidence of severe hepatic decompensation at the time of enrollment
• Patients taking probenecid medication within 1 week prior to study day 1 or during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Tamiflu; 10 doses over 5 or 6 days of which the first 5 or 6 doses must be intravenous, up to 5 days (10 doses) of additional intravenously or oral treatment if virus shedding continues at day 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4	Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2	Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4	Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate		Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate		Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate		Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values	IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either ≥5 times change in the NAI IC50 visit value from the Reference value at a visit or ≥5 times change in the NAI IC50 Visit value from the Baseline value.	Baseline, Days 1, 3, 4, 6, 15
Number of Participants With Oseltamivir Resistance Mutation	Resistance was assessed by neuraminidase (NA) and hemagglutinin (HA) genes sequencing analysis, using Reverse Transcription Polymerase Chain Reaction (RT-PCR).	Up to Day 30

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Munoz FM, Anderson EJ, Deville JG, Clinch B, Kamal MA. Pharmacokinetics and safety of intravenous oseltamivir in infants and children in open-label studies. Int J Clin Pharmacol Ther. 2015 Jul;53(7):531-40. doi: 10.5414/CP202307.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 20, 2010
• First Submitted That Met QC Criteria: January 20, 2010
• First Posted (Estimate): January 21, 2010

Study Record Updates

• Last Update Posted (Estimate): July 27, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: NP25138